The "mini-epidemic" distribution of rare conditions (either sporadic, inherited or due to a transmissible agent) is frequently described as a cluster. Genetic abnormalities and environmental factors are usually investigated to explain the presence of a disease cluster. We have reported a cluster of amyotrophic lateral sclerosis (ALS) cases in a small area of central Italy, where an identical SOD1 gene mutation was found both in familial ALS (FALS) cases and in one apparently sporadic ALS individuals. Along with this cluster of ALS patients, we review important clusters of neurological disorders in Italy and discuss the importance of an accurate estimation of their regional/local prevalence. This approach is likely to facilitate molecular investigations, the search for environmental agents and the analysis of gene-environment interaction in disease presentation and development. The organisation of national registers that record, in particular, the geographical distribution of neurological disorders, might represent a good research strategy.